Faculty Collaboration Database

Age-related decrease in 15-lipoxygenase contributes to reduced vasorelaxation in rabbit aorta. Am J Physiol Heart Circ Physiol 2008 Feb;294(2):H679-87

Date

12/07/2007

Pubmed ID

18055513

DOI

10.1152/ajpheart.01053.2007

Scopus ID

2-s2.0-39149144510 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Rabbit 15-lipoxygenase-1 (15-LO-1) oxygenates arachidonic acid (AA) into 15-hydroperoxyeicosatetraenoic acid, which is then converted to the vasodilatory 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA). We studied the age-dependent expression of the 15-LO-1 in rabbit aorta and its effects on the synthesis of THETA, HEETA, and vasoactivity. Aortas of 1-wk-old rabbits express greater amounts of 15-LO-1 mRNA and protein compared with aortas of 4-, 8-, or 16-wk-old rabbits. The synthesis of THETA and HEETA in the rabbit aorta was also reduced with age. THETA synthesis was maximal in 1-wk-old aortas but decreased in aortas of 4- (42%), 8- (4%), and 16-wk-old (1%) rabbits. Similarly, THETA and HEETA synthesis decreased with age in mesenteric arteries from 1-, 4-, 8-, and 16-wk-old rabbits. The maximum vasorelaxation response to acetylcholine (10(-6) M) in the presence of indomethacin and nitro-l-arginine decreased in the order of 1 wk (64.5 +/- 6.9%), 4 wk (52.6 +/- 8.9%), 8 wk (53.0 +/- 9.4%), and 16 wk (33.3 +/- 6.6%). Similarly, the maximum relaxation to AA (3 x 10(-4) M) decreased with age in the order of 1 wk (60.4 +/- 8.9%), 4 wk (56.3 +/- 5.8%), 8 wk (41.8 +/- 12.3%), and 16 wk (28.9 +/- 1.6%). In contrast, the vasorelaxation to sodium nitroprusside was not significantly altered by age. These data indicate that aortic 15-LO-1 expression and activity are downregulated with aging in rabbits. This decrease is paralleled by the reduced synthesis of vasoactive THETA and HEETA and aortic relaxations to acetylcholine and AA.

Author List

Tang X, Aggarwal N, Holmes BB, Kuhn H, Campbell WB

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Acetylcholine
Aging
Amino Acid Sequence
Animals
Animals, Newborn
Aorta
Arachidonate 15-Lipoxygenase
Arachidonic Acid
Biological Factors
Blotting, Western
Cloning, Molecular
In Vitro Techniques
Kinetics
Molecular Sequence Data
Muscle Relaxation
Muscle, Smooth, Vascular
Nitroprusside
RNA
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Vasodilator Agents